We propose to undertake a broad multidisciplinary approach to drug abuse problems. Chemical, biochemical, pharmacological, physiological, and behavioral techniques will be used to explore marihuana, the narcotics and narcotic-antagonists, the inhalants, and other classes of abused substances. Specific binding of the cannabinoids; the role of neurotransmitters, Ca ions and cyclic-GMP in the action of the narcotics and narcotic antagonists; and the development of new methods for the study of the behavior effects of inhalants, and abuse potential will be stressed. Considerable emphasis will also be placed on the pharmacology of the cannabinoids, their behavioral interactions, and the role of pharmacokinetics and metabolism in these processes. New narcotics, narcotic antagonists, and cannabinoids will be synthesized in an effort to gain a greater insight into how these drug classes act. Of particular interest will be the study of d-morphine, d-codenine and d-naloxone. We also propose extensive studies on the abuse potential and pharmacokinetics of LAAM and its metabolites.